Type 2 diabetes mellitus (T2DM) is one of the most common, chronic, and life threatening diseases. Every year, the prevalence of T2DM is increasing worldwide and recently, World Health Organization (WHO) predicted that by 2030, the number of patients diagnosed with T2DM will be more than 366 millions. Clinically T2DM is characterized by increased blood glucose levels, either because of defect in insulin secretion, insulin resistance or both.
US 2004/0009976 A1 discloses a compound of Formula (A1):
and their use for the treatment of Type II diabetes and stimulating insulin secretion in mammals. US 2003/0109550 A1 discloses a compound of formula A2,
wherein, B is a 5 or 6 saturated or unsaturated heterocyclic wherein said heterocyclic is optionally substituted with R1, R2, and R12; X is selected from the group consisting of: N and C; Y and Z are independently selected from the group consisting of: N, CH, CR3, S, and O; R3 is selected from the group consisting of: substituted or unsubstituted amidine, alkylamino, aminoalkyl, CONHR7, NH2, NHCOR6, and CH2NHCOR6.
EP 0418845 B1 discloses novel Pyrazole derivatives, processes for preparation thereof and pharmaceutical composition comprising the same. It provides a compound of the formula A3:

Wherein, R1 is aryl which may be substituted with substituent(s) selected from the group consisting of 40 lower alkyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, hydroxy, lower alkylsulfonyloxy, nitro, amino, lower alkylamino, acylamino and lower alkyl-(acyl)amino; or a heterocyclic group; R2 is hydrogen; methyl substituted with amino, lower alkylamino, halogen or acyloxy; acyl; 45 acylamino; cyano; halogen; lower alkylthio; lower alkylsulfinyl; or a heterocyclic group; and R3 is aryl substituted with lower alkyl, lower alkylthio, lower alkylsulfinyl, halogen, amino, lower alkylamino, acylamino, lower alkyl(acyl)amino, lower alkoxy, cyano, hydroxy or acyl; or a heterocyclic group which may be substituted with lower alkylthio, lower alkylsulfinyl or 50 lower alkylsulfonyl.
U.S. Pat. No. 4,436,913 discloses 1H- and 2H-indazole derivatives and pharmaceuticals containing these blood-pressure lowering 1H- and 2H indazole derivatives of the formula A4,
and their acid addition salts, wherein R1 may be in position 1 or position 2 on the nitrogen atoms in formula 1. The groups R1, R2 and R3 represent hydrogen or the usual lower molecular groups. The R group is a 2 imidazolinylamino group or a 3,4,5,6-tetryhydropyrimidinylamino group, wherein these groups may also be present in their tautomeric forms. These groups may also be in an aryl group in the R1 group, in which case the R group may also be a halogen atom. R may only represent one of the heterocyclic secondary or tertiary amino groups in the 4 or 7th position for the 1H indazole derivatives when the R1 group is simultaneously an aryl or an aralkyl group. U.S. Pat. No. 6,878,735 B2 discloses an imidazoline of the formula A5,

Wherein R1 is aryl, optionally substituted, R2 is selected from the group consisting of alkyl, acyl, aryl, aralkyl, heteroaryl containing 5 to 14 ring members, and heterocyclic containing 5 to 12 ring members; R3 is aryl, optionally substituted, R4 is aralkyl, optionally substituted, and R5 is selected from the group consisting of hydrogen and an alkyl group, all of Which are optionally substituted.
U.S. Pat. No. 7,541,376 B2 provides a novel 1H-indazole compound having an excellent JNK inhibitory action. More specifically, it provides a compound represented by the formula A6,

Wherein R1 is a C6-C14 aromatic cyclic hydrocarbon group etc.; R2, Wand R5 each independently represent a hydrogen atom, a halogen atom, a cyano group etc.; L is a single bond, or a C1-C6 alkylene group etc.; X is a single bond, or a group represented by —CO—NH— or —NH—, CO—, etc.; and Y is a C3-C8 cycloalkyl group, a C6-C14 aromatic cyclic hydrocarbon group or a 5- to 14-membered aromatic heterocyclic group etc., a salt thereof or a hydrate of them.
US 2011/0034441 A1 discloses a compound of formula A7,
wherein R1, R2, R4, R5, R6, Wand R8 are independently selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —(C1-9 alkyl)ncarbocyclylR12, —(C1-9 alkyl)nheterocyclylR12, —(C1-9 alkyl)narylR12, —(C1-9 alkyl)nheteroarylR12, —(C1-9 alkyl)nOR9, —(C1-9 alkyl)nSR9, —(C1-9 alkyl)nS(═O)R10, —(C1-9 alkyl)nSO2R9, —(C1-9 alkyl)nN(R9)S(═O)R10, —(C1-9 alkyl)nN(R9)SO2R9, —(C1-9 alkyl)nSO2N(R9)2, —(C1-9 alkyl)nN(R9)2, —(C1-9 alkyl)nN(R9)C(=A)N(R9)2, —(C1-9 alkyl)nNR9C(═O)OR9, —(C1-9 alkyl)nC(=A)N(R9)2, —(C1-9 alkyl)nN(R9)C(=A)R9, —(C1-9 alkyl)nOC(═O)N(R9)2, —NO2, —CN, —(C1-9 alkyl)nCO2R9 and —(C1-9 alkyl)nC(=A)R9.
US 2002/0161022 A1 discloses a compound of formula A8,

Wherein R1 is a substituted or unsubstituted alkyl, aryl, heteroaryl, carbocycle, heterocycle etc.; R2 is a substituted or unsubstituted alkyl, aryl, heteroaryl, carbocycle, heterocycle etc.
WO2011057959 discloses a compound of formula A9,
wherein, R1, R2, R3, independently of each other; is hydrogen, halogen, lower alkyl or alkoxy; R4 is hydrogen, unsubstituted lower alkyl, or lower alkyl substituted with one to four substituents independently selected from the group consisting of methyl, (=0) and —COOH; X is CH or N; and Y is hydrogen or —NH2, or a pharmaceutically acceptable salt thereof. Further, it relates to the use of compound A9, or a pharmaceutically acceptable salt thereof, for the treatment or prophylaxis of metabolic diseases and disorders.
Article titled, “2-(4,5-Dihydro-1H-imidazol-2-yl)indazole (indazim) derivatives as selective 12 imidazoline receptor ligands” by F. Saczewski et al. in European Journal of Pharmaceutical Sciences 20 (2003) 201-208 reports the synthesis of a series of variously substituted 2-(4,5-dihydro-1H-imidazol-2-yl)indazoles and 2-(4,5-dihydro-1H-imidazol-2-yl)-4,5,6,7-tetrahydroindazole. Further, it reports that 4-Chloro-2-(4,5-dihydro-1H-imidazol-2-yl)indazole (3f, 4-Cl-indazim) which shows good affinity at imidazoline I2 receptor and unprecedented among this type of imidazoline ligands low affinity at alpha-2-adrenoceptor.
Article titled, “Click” synthesis of small molecule-peptide conjugates for organelle-specific delivery and inhibition of lysosomal cysteine proteases” By YuhuiLoh in ChemCommun (Camb). 2010 Nov. 28; 46 (44):8407-9 reports a click chemistry approach for the synthesis of small molecule inhibitor-peptide conjugates to achieve organelle-specific delivery. It further provides a process where COOH group was converted to —CONNH2ME using N-methylmorpholine (NMM) isobutyl chloroformate (ISCF) and Methylhydrazine salt.
Article, “Carboxylic Compounds, Nitriles, and Their Interconversion” in Organic Mechanisms, 2010, pp 321-338 reports Trifluoroacetic acid anhydride-mediated dehydration of pivalic acid amide (A) to pivalic acid nitrile (B) with the reagent forming trifluoroacetic acid F3C—CO2H.
Article titled, “Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines” by Rajesh H. Bahekar, Mukul R. Jain, Pradip A. Jadav, Vijay M. Prajapati, Dipam N. Patel, Arun A. Gupta, Ajay Sharma, Robby Tom, Debdutta Bandyopadhya, Honey Modi and Pankaj. R. Patel in Bioorganic & Medicinal Chemistry 15 (2007) 6782-6795 reports the conversion of nitriles to imidazoline using ethylene diamine, P2S5 at 120° C. and 5 hrs.
The drugs used in the diabetes therapy belong to the following therapeutic classes, defined on the basis of the pathogenetic role of the insulin resistance (Trends in Pharm. Sci. 21, 259-265 2000): insulin, sulphonylureas, metformin, inhibitors of alpha-glycosidase (acarbose) and thiazolidinediones (troglitazone). Insulin is the most known drug and it is considered the reference drug in diabetes treatment. But, insulin therapy suffers from the following drawbacks: the drug is administrable only by parenteral route, it is necessary to constantly control the glycaemia levels, local allergic reactions can arise, insulin resistance compels to meaningfully increase the drug dosage during the time, the local tolerability is poor.
Also the other therapeutical approaches are not without drawbacks, sometimes even remarkable. For example sulphonylureas, which are administered alone or in combination with insulin or with other oral hypoglycemizing drugs, can cause hypoglycemia. Metformin, which is used alone or in combination with sulphonylurea, is contraindicated in the presence of renal and hepatic diseases, and can induce a state of lactic acidosis. Acarbose is used alone or in combination with sulphonylurea for reducing the postprandial glycemic levels, but it often induces side effects at the gastrointestinal system level. Troglitazone, which is only used in combination with insulin, can induce hepatotoxic effects.
Thus, there is an urgent need to develop some novel therapeutic approaches for glycemic control that can attempt to preserve normal physiological response to meal intake. One such approach is based on the development of insulin secretagogues, which do not cause glucose secretion under basal blood glucose levels but show only glucose-dependent insulin release.
Considering the standing problems in the prior art and long felt need of a new drug which shows glucose dependent insulin release, overcoming side-effects for treatment of diabetes or diabetes related complications inventors have come up with the current invention. The current invention discloses novel indazole compounds, derivatives thereof and method to synthesize the same. The compounds show anti diabetic activity against both type 1 and type 2 diabetes and related complications like diabetic neuropathy, diabetic retinopathy and a variety of vascular diseases which are results of continued fluctuating glucose blood levels.